The third edition of The Parathyroids, led by a new stellar editorial team, has been thoroughly updated to reflect the considerable advances in just about every aspect of PTH biology over the past decade. It continues to be the authoritative reference that spans the basic science of parathyroid hormone treatment to major clinical disorders in a superb, single compendium. This translational resource is invaluable to graduate students, fellows, researchers, and research clinicians in the fields of endocrinology, bone biology, osteology, and rheumatology.
- Contains chapters and information on noninvasive imaging, fracture healing, secondary diseases such as CKD, Vitamin D, cell signaling pathways, vascular calcification, as well as advances in genetics/genomics
- Includes essential updates on the critical importance of Vitamin D insufficiency and its relationship to secondary hyperparathyroidism
- Offers new insights into the underlying mechanisms of parathyroid hormone actions on osteocytes and sclerostin
- Examines essential updates in the understanding of secondary hyperparathyroidism associated with chronic kidney disease, facture healing, and vascular disease
Inhaltsverzeichnis
1;Front Cover;1 2;The Parathyroids: Basic and clinical concepts;4 3;Copyright;5 4;Contents;6 5;Contributors;16 6;Preface to the Third Edition;20 7;Preface to the Second Edition;22 8;Preface to the First Edition;24 9;Introduction - A History of the Parathyroid Glands and their Secretory Product, Parathyroid Hormone;28 9.1;PREHISTORIC DEVELOPMENT;28 9.2;DISCOVERY OF THE PARATHYROID GLANDS;29 9.3;DISCOVERY OF THE PARATHYROIDS ACTIVE PRINCIPLE;32 9.4;THE SEARCH FOR MECHANISMS OF PTH ACTION;33 9.5;MODERN APPROACHES TO PTH STRUCTURE AND FUNCTION;35 9.6;PRIMARY HYPERPARATHYROIDISMA NEW DISEASE;37 9.7;HUMORAL HYPERCALCEMIA OF MALIGNANCY AND THE DISCOVERY OF PARATHYROID HORMONE-RELATED PROTEIN (PTHRP);40 9.8;REDISCOVERY OF THE ANABOLIC EFFECT OF PTH;40 9.9;PTH: A TREATMENT FOR OSTEOPOROSIS;41 9.10;CONCLUSION;44 9.11;References;44 10;Section I - Molecular, Cellular, and Physiologic Aspects of The Parathyroids;48 10.1;Chapter 1 - Parathyroids: Morphology and Pathology;50 10.1.1;Morphology and Pathology;50 10.1.2;INTRODUCTION;50 10.1.3;EMBRYOLOGY;50 10.1.4;ANATOMY AND HISTOLOGY;50 10.1.5;HYPERPARATHYROIDISM;51 10.1.6;FAMILIAL HYPERPARATHYROIDISM;56 10.1.7;UNUSUAL LESIONS OF THE PARATHYROID;56 10.1.8;INTRAOPERATIVE ASSESSMENT OF PARATHYROIDOLD AND NEW;57 10.1.9;SPECIAL STUDIES AND THE PARATHYROID;58 10.1.10;HUMORAL HYPERCALCEMIA OF MALIGNANCY;58 10.1.11;HYPOPARATHYROIDISM;58 10.1.12;References;59 10.2;Chapter 2 - Parathyroid Hormone Gene: Structure, Evolution, and Regulation;64 10.2.1;Structure, Evolution, and Regulation;64 10.2.2;INTRODUCTION;64 10.2.3;PREPROPTH;64 10.2.4;GENE STRUCTURE;65 10.2.5;EVOLUTION;66 10.2.6;REGULATION;67 10.2.7;References;69 10.3;Chapter 3 - Parathyroid Hormone-related Protein: Gene Structure, Biosynthesis, Metabolism and Regulation;72 10.3.1;Gene Structure, Biosynthesis, Metabolism and Regulation;72 10.3.2;INTRODUCTION;72 10.3.3;ISOLATION AND CLONING OF PTHRP;72 10.3.4;GENE STRUCTURE;74 10.3.5;TRANSCRIPTIONAL REGULATION AND MRNA SPLICING;76 10.3.6;PRO
TEIN STRUCTURE AND POSTTRANSLATIONAL PROCESSING;79 10.3.7;NUCLEAR IMPORT AND INTRACRINE FUNCTION OF PTHRP;81 10.3.8;TISSUE DISTRIBUTION AND PARACRINE FUNCTION;82 10.3.9;CONCLUSION;85 10.3.10;References;85 10.4;Chapter 4 - Interactions of PTH with Receptors and Signaling;92 10.4.1;INTRODUCTION;92 10.4.2;PARATHYROID HORMONELIGAND DETERMINANTS OF BIOLOGICAL ACTIVITY;93 10.4.3;THE PTHR1 CLONING, GENE CHARACTERIZATION, AND EVOLUTION;95 10.4.4;STRUCTURAL FEATURES OF THE PTHR1 AND MODE OF LIGAND BINDING;97 10.4.5;LIGAND INTERACTIONS TO THE RECEPTORS N-TERMINAL EXTRACELLULAR DOMAIN (ECD);98 10.4.6;THE PTHR1 TRANSMEMBRANE DOMAIN (TMD) REGION, STRUCTURE, AND MODE OF ACTION;99 10.4.7;MECHANISMS OF SIGNALING TRANSDUCTION AND SIGNAL REGULATION;100 10.4.8;MECHANISM OF CONFORMATIONAL CHANGE AND PROLONGED SIGNALING AT THE PTHR1;101 10.4.9;SMALL MOLECULE LIGANDS FOR THE PTHR;102 10.4.10;References;103 10.5;Chapter 5 - Interactions of PTHrP with Receptors and Signaling;108 10.5.1;INTRODUCTION;108 10.5.2;STRUCTURES OF THE PTHRP GENE, MRNA, AND PEPTIDES;109 10.5.3;N-TERMINAL PTHRP AND RECEPTORS;112 10.5.4;MID-MOLECULAR PTHRP AND RECEPTORS;114 10.5.5;NUCLEAR/NUCLEOLAR PTHRP AND ITS RECEPTORS;116 10.5.6;C-TERMINAL PTHRP AND ITS RECEPTORS;118 10.5.7;CONCLUSIONS;120 10.5.8;References;122 10.6;Chapter 6 - Control of Parathyroid Hormone Secretion by its Key Physiological Regulators;128 10.6.1;INTRODUCTION;128 10.6.2;IMPORTANCE OF PTH IN MAINTAINING MINERAL ION HOMEOSTASIS IN VIVO;128 10.6.3;GENERAL MECHANISMS DETERMINING THE OVERALL RATE OF PTH SECRETION;131 10.6.4;CELLULAR AND MOLECULAR MECHANISMS BY WHICH REGULATES THE VARIOUS ASPECTS OF PARATHYROID FUNCTION DETERMINING THE OVERALL RATE OF...;132 10.6.5;REGULATION OF OVERALL PARATHYROID FUNCTION BY 1,25(OH)2D3;138 10.6.6;REGULATION OF OVERALL PARATHYROID SECRETORY FUNCTION BY PHOSPHATE;139 10.6.7;EFFECTS OF FGF23 ON OVERALL PARATHYROID FUNCTION;140 10.6.8;CONCLUSIONS;141 10.6.9;References;141 10.7;Chapter 7 - Molecular Actions of Parathyro
id Hormone;146 10.7.1;INTRODUCTION;146 10.7.2;PTH SIGNAL TRANSDUCTION;146 10.7.3;PTH REGULATION OF GENE TRANSCRIPTION;148 10.7.4;CONTROL OF CELL PROLIFERATION AND SURVIVAL BY PTH;149 10.7.5;REGULATION OF ION TRANSPORT BY PTH;150 10.7.6;References;150 10.8;Chapter 8 - Cellular Actions of PTH: Osteoblasts, Osteoclasts, and Osteocytes;154 10.8.1;Osteoblasts, Osteoclasts, and Osteocytes;154 10.8.2;INTRODUCTION;154 10.8.3;CELLULAR ACTIONS OF PTH ON BONE;154 10.8.4;CONCLUSION;160 10.8.5;References;160 10.9;Chapter 9 - Physiologic Actions of PTH I: PTH Action on the Skeleton;166 10.9.1;PTH Action on the Skeleton;166 10.9.2;INTRODUCTION;166 10.9.3;PHYSIOLOGIC, PHARMACOLOGIC, AND PATHOLOGIC INTERACTIONS OF PTH WITH THE SKELETON;167 10.9.4;MOLECULAR AND CELLULAR MECHANISMS OF ACTION;169 10.9.5;CONTRIBUTIONS TO MODELING AND REMODELING OF THE SKELETON;172 10.9.6;SUMMARY;174 10.9.7;References;174 10.10;Chapter 10 - Physiological Actions of PTH II: Renal Actions;180 10.10.1;Renal Actions;180 10.10.2;INTRODUCTION;180 10.10.3;NEPHRON SITES OF PTH ACTION;180 10.10.4;PTH ACTIONS ON ION TRANSPORT;183 10.10.5;PTH EFFECTS ON METABOLISM;186 10.10.6;PTH METABOLISM BY THE KIDNEY;187 10.10.7;Acknowledgments;188 10.10.8;References;188 10.11;Chapter 11 - Physiological Actions of PTH and PTHrP III: Endochondral Bone Formation;192 10.11.1;Endochondral Bone Formation;192 10.11.2;Endochondral Bone Formation;192 10.11.3;THE PTHRPINDIAN HEDGEHOG PATHWAY IN THE GROWTH PLATE;195 10.11.4;ACTIONS OF PTHRP DURING BONE DEVELOPMENT;198 10.11.5;ACTIONS OF INDIAN HEDGEHOG DURING BONE DEVELOPMENT;202 10.11.6;ROLES OF IHH, PTHRP, AND PTHR1 IN THE POSTNATAL SKELETON;205 10.11.7;CONCLUSION;208 10.11.8;References;208 10.12;Chapter 12 - Physiological Actions of PTH and PTHrP IV: Vascular, Cardiovascular, and CNS Biology;214 10.12.1;Vascular, Cardiovascular, and CNS Biology;214 10.12.2;INTRODUCTION;214 10.12.3;PTH/PTHRP BIOLOGY IN CARDIOVASCULAR DEVELOPMENT;214 10.12.4;PTHR SIGNALING IN ARTERIAL BIOLOGY: VASCULAR
SMOOTH MUSCLE CELL AND ENDOTHELIAL RESPONSES TO PTH AND PTHRP;215 10.12.5;TIP39 IN VASCULAR PHARMACOLOGY AND POTENTIAL CONTRIBUTIONS OF CNS TIP39 AND PTHRP TO CARDIOVASCULAR MEDICINE;217 10.12.6;IMPACT OF HYPERPARATHYROIDISM ON CARDIOVASCULAR MORTALITY, CORONARY FLOW RESERVE, AND VASCULAR STIFFNESS: AN EMERGING CONCERN IN...;218 10.12.7;SECONDARY HYPERPARATHYROIDISM OF CHRONIC KIDNEY DISEASE (CKD); THE METABOLIC PERFECT STORM OF CARDIOVASCULAR RISK;219 10.12.8;IMPACT OF PTH AND HYPERPARATHYROIDISM ON CALCIFIC AORTIC VALVE DISEASE (CAVD): A SCLEROTIC CONUNDRUM;221 10.12.9;CHRONIC PTH1R ACTIVATION AND THE RENINANGIOTENSINALDOSTERONE (RAA) AXIS IN CARDIOVASCULAR DISEASE: A FEED-FORWARD VICIOUS CYCL...;221 10.12.10;PTH/PTHRP SIGNALING AND THE BONEVASCULAR AXIS;221 10.12.11;CONCLUSIONS AND FUTURE DIRECTIONS;223 10.12.12;Acknowledgments;223 10.12.13;References;223 10.13;Chapter 13 - Physiological Actions of Parathyroid Hormone (PTH) and PTH-related Protein: Epidermal, Mammary, Reproductive, and Pancreatic Tissues;230 10.13.1;Epidermal, Mammary, Reproductive, and Pancreatic Tissues;230 10.13.2;INTRODUCTION;230 10.13.3;SKIN;230 10.13.4;MAMMARY GLAND;232 10.13.5;REPRODUCTIVE TISSUES;237 10.13.6;ENDOCRINE PANCREAS;241 10.13.7;CONCLUSION;243 10.13.8;Acknowledgments;243 10.13.9;References;243 10.14;Chapter 14 - PTH and T-cell Biology;250 10.14.1;EFFECTS OF PTH IN BONE;250 10.14.2;T-CELL SUBSETS AND THEIR ROLE IN BONE HOMEOSTASIS;251 10.14.3;T CELLS AND PTH-INDUCED BONE LOSS;252 10.14.4;ROLE OF T CELLS IN THE ANABOLIC ACTIVITY OF INTERMITTENT PTH TREATMENT;253 10.14.5;ROLE OF T CELLS ON THE EXPANSION OF HSCS INDUCED BY PTH;255 10.14.6;CONCLUSIONS;256 10.14.7;References;256 10.15;Chapter 15 - Anabolic and Catabolic Pathways of Parathyroid Hormone on the Skeleton;260 10.15.1;INTRODUCTION;260 10.15.2;PTH SIGNALING;260 10.15.3;ACTIONS OF PTH THAT CONTRIBUTE TO INCREASED BONE RESORPTION: CATABOLIC;261 10.15.4;ACTIONS OF PTH CONTRIBUTING TO INCREASED BONE FORMATION: ANABOLIC;262 10.15
.5;GENE PROFILE IN CATABOLIC AND ANABOLIC PTH REGIMES;265 10.15.6;THE ROLE OF T CELLS ON THE ANABOLIC AND CATABOLIC ACTIONS OF PTH;265 10.15.7;THE INFLUENCE OF BONE RESORPTION ON PTH-INDUCED BONE ANABOLISM;267 10.15.8;SUMMARY;267 10.15.9;References;268 10.16;Chapter 16 - Metabolism and Measurement of Parathyroid Hormone;272 10.16.1;THE CIRCULATING PARATHYROID HORMONE (PTH) PARADOX;272 10.16.2;FIRST-GENERATION PTH ASSAYS: CIRCULATING PTH IMMUNOHETEROGENEITY;272 10.16.3;SECOND-GENERATION PTH ASSAYS: IMMUNORADIOMETRIC (IRMA) ASSAYS;272 10.16.4;THIRD-GENERATION PTH ASSAY: IMPROVED IRMA;273 10.16.5;ORIGIN OF CIRCULATING PTH MOLECULAR FORMS;273 10.16.6;REGULATION OF CIRCULATING PTH MOLECULAR FORMS;273 10.16.7;MOLECULAR FORMS OF PTH ASSOCIATED WITH SPECIFIC CLINICAL CONDITIONS;274 10.16.8;CONCLUSION;276 10.16.9;References;277 11;Section II - Clinical Aspects of Primary Hyperparathyroidism;280 11.1;Chapter 17 - Parathyroid Growth: Normal and Abnormal;282 11.1.1;Normal and Abnormal;282 11.1.2;INTRODUCTION AND BACKGROUND;282 11.1.3;ABNORMAL PARATHYROID GROWTH;286 11.1.4;INTEGRATION OF PARATHYROID GROWTH AND HORMONE SECRETION;298 11.1.5;Acknowledgments;299 11.1.6;References;299 11.2;Chapter 18 - Molecular Basis of Primary Hyperparathyroidism;306 11.2.1;INTRODUCTION;306 11.2.2;CLONALITY OF PARATHYROID TUMORS;307 11.2.3;SPECIFIC GENETIC ABNORMALITIES IN BENIGN PARATHYROID TUMORS;308 11.2.4;OTHER GENETIC ABNORMALITIES IN SPORADIC PARATHYROID TUMORS;314 11.2.5;MOLECULAR PATHOGENESIS OF PARATHYROID CARCINOMA;314 11.2.6;EPIGENETICS AND GENE EXPRESSION ALTERATIONS IN SPORADIC PARATHYROID ADENOMAS;316 11.2.7;ECTOPIC SECRETION OF PTH;317 11.2.8;SUMMARY;318 11.2.9;References;318 11.3;Chapter 19 - Epidemiology of Primary Hyperparathyroidism;324 11.3.1;INTRODUCTION;324 11.3.2;INCIDENCE AND PREVALENCE;324 11.3.3;SPECIAL POPULATION CONSIDERATIONS IN SPORADIC PRIMARY HYPERPARATHYROIDISM;326 11.3.4;CLINICAL FEATURES;327 11.3.5;MORTALITY;328 11.3.6;COST OF PRIMARY HYPERPARATHYROIDISM;329 11.3.
7;SUMMARY AND CONCLUSION;331 11.3.8;Acknowledgment;331 11.3.9;References;331 11.4;Chapter 20 - Clinical Presentation of Primary Hyperparathyroidism: A Global Perspective;336 11.4.1;A Global Perspective;336 11.4.2;INTRODUCTION;336 11.4.3;PRESENTATION IN THE UNITED STATES;336 11.4.4;PRESENTATION IN EUROPE;337 11.4.5;PRESENTATION IN LATIN AMERICA;337 11.4.6;PRESENTATION IN ASIA;338 11.4.7;BONE DISEASE IN PRIMARY HYPERPARATHYROIDISM;338 11.4.8;NEPHROLITHIASIS IN PRIMARY HYPERPARATHYROIDISM;339 11.4.9;NON-CLASSICAL MANIFESTATIONS OF PRIMARY HYPERPARATHYROIDISM;339 11.4.10;DIAGNOSIS OF PRIMARY HYPERPARATHYROIDISM;340 11.4.11;References;341 11.5;Chapter 21 - Asymptomatic Primary Hyperparathyroidism;344 11.5.1;INTRODUCTION;344 11.5.2;INCIDENCE AND PATHOGENESIS OF PRIMARY HYPERTHYROIDISM;344 11.5.3;CLINICAL PRESENTATION OF PRIMARY HYPERPARATHYROIDISM: THEN AND NOW;345 11.5.4;DIAGNOSIS AND BIOCHEMICAL CHARACTERIZATION OF ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM;346 11.5.5;CLASSICAL ORGAN INVOLVEMENT IN ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM;348 11.5.6;NON-CLASSICAL ORGAN INVOLVEMENT IN ASYMPTOMATIC PHPT;351 11.5.7;PRIMARY HYPERPARATHYROIDISM: YESTERDAY, TODAY, AND TOMORROW;353 11.5.8;References;354 11.6;Chapter 22 - Normocalcemic PHPT;358 11.6.1;INTRODUCTION;358 11.6.2;PATHOPHYSIOLOGY;358 11.6.3;DIAGNOSIS;359 11.6.4;EPIDEMIOLOGY;360 11.6.5;CLINICAL PRESENTATION;361 11.6.6;NATURAL HISTORY;363 11.6.7;MANAGEMENT;364 11.6.8;SUMMARY AND CONCLUSIONS;364 11.6.9;Acknowledgments;364 11.6.10;References;364 11.7;Chapter 23 - Familial and Hereditary Forms of Primary Hyperparathyroidism;368 11.7.1;INTRODUCTION;368 11.7.2;SYNDROMIC FORMS OF PHPT;368 11.7.3;NON-SYNDROMIC (ISOLATED) FORMS OF PHPT;381 11.7.4;GENE TESTING IN CLINICAL PRACTICE FOR PHPT PATIENTS;383 11.7.5;CONCLUSIONS;385 11.7.6;Acknowledgments;385 11.7.7;References;385 11.8;Chapter 24 - Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism;392 11.8.1;HISTORICAL PERSPECTIVE AND NOMENCLATURE;392 11.8.2;CL
INICAL CHARACTERISTICS OF FHH;393 11.8.3;LABORATORY AND DYNAMIC STUDIES IN FHH;394 11.8.4;GENETICS AND MOLECULAR GENETICS OF FHH;399 11.8.5;GENOTYPEPHENOTYPE ASSOCIATIONS;404 11.8.6;DIAGNOSIS AND MANAGEMENT OF FHH;405 11.8.7;CLINICAL CHARACTERISTICS OF NEONATAL HYPERPARATHYROIDISM;406 11.8.8;GENETICS AND MOLECULAR GENETICS OF NEONATAL HYPERPARATHYROIDISM, INCLUDING NEONATAL SEVERE HYPERPARATHYRODISM;407 11.8.9;DIAGNOSIS AND MANAGEMENT OF NHPT AND NSHPT;408 11.8.10;CONCLUSIONS;409 11.8.11;Acknowledgments;409 11.8.12;References;409 11.9;Chapter 25 - Primary Hyperparathyroidism in Children and Adolescents;416 11.9.1;INTRODUCTION;416 11.9.2;ETIOLOGY OF PEDIATRIC PRIMARY HYPERPARATHYROIDISM;419 11.9.3;PATHOLOGY;422 11.9.4;CLINICAL FEATURES AND COMPLICATIONS;422 11.9.5;ASCERTAINMENT AND DIAGNOSIS;422 11.9.6;MANAGEMENT AND OUTCOME;423 11.9.7;OUTCOMES;424 11.9.8;SUMMARY;424 11.9.9;References;424 11.10;Chapter 26 - Acute Primary Hyperparathyroidism;428 11.10.1;Acute Primary Hyperparathyroidism;428 11.10.2;RISK OF DEVELOPING ACUTE PRIMARY HYPERPARATHYROIDISM;428 11.10.3;DEMOGRAPHICS;429 11.10.4;LABORATORY EVALUATION;429 11.10.5;TARGET ORGAN MANIFESTATIONS;431 11.10.6;PATHOLOGY;431 11.10.7;PATHOPHYSIOLOGY;432 11.10.8;ACUTE PARATHYROID CRISIS ASSOCIATED WITH PREGNANCY;432 11.10.9;OTHER ASSOCIATIONS WITH ACUTE PRIMARY HYPERPARATHYROIDISM;432 11.10.10;ANIMAL MODELS OF ACUTE PRIMARY HYPERPARATHYROIDISM;432 11.10.11;TREATMENT;433 11.10.12;OUTCOMES;433 11.10.13;SUMMARY;434 11.10.14;References;434 11.11;Chapter 27 - Parathyroid Carcinoma;436 11.11.1;INTRODUCTION;436 11.11.2;EPIDEMIOLOGY;436 11.11.3;ETIOLOGY;436 11.11.4;PATHOGENESIS;437 11.11.5;PATHOLOGY;438 11.11.6;CLINICAL FEATURES;440 11.11.7;IMAGING STUDIES;441 11.11.8;NATURAL HISTORY AND SURVEILLANCE;442 11.11.9;MANAGEMENT;442 11.11.10;MANAGEMENT OF HYPERCALCEMIA;444 11.11.11;PROGNOSIS;445 11.11.12;CLOSING REMARKS;445 11.11.13;References;445 11.12;Chapter 28 - Bone Turnover Markers in Primary Hyperparathyroidism;450 11.12.1;INTRO
DUCTION;450 11.12.2;BONE TURNOVER MARKERS;450 11.12.3;MANAGEMENT OF PHPT AND EFFECTS ON BONE TURNOVER MARKERS;451 11.12.4;CONCLUSION;453 11.12.5;References;454 11.13;Chapter 29 - Bone Histomorphometry and Bone Quality in Primary Hyperparathyroidism;456 11.13.1;INTRODUCTION;456 11.13.2;BONE HISTOMORPHOMETRY: STATIC AND DYNAMIC INDICES;456 11.13.3;BONE TURNOVER IN PRIMARY HYPERPARATHYROIDISM;457 11.13.4;BONE MASS IN PRIMARY HYPERPARATHYROIDISM;458 11.13.5;BONE STRUCTURE IN PRIMARY HYPERPARATHYROIDISM;460 11.13.6;MECHANISM OF MAINTENANCE OF CANCELLOUS BONE VOLUME AND STRUCTURE AT THE ILIAC CREST;463 11.13.7;EFFECTS OF PARATHYROIDECTOMY ON BONE STRUCTURE AND REMODELING ACTIVITY IN THE ILIAC CREST;466 11.13.8;EFFECTS OF PRIMARY HYPERPARATHYROIDISM ON MATERIAL PROPERTIES OF BONE MATRIX;467 11.13.9;CONCLUSION;470 11.13.10;Acknowledgments;470 11.13.11;References;470 11.14;Chapter 30 - Skeletal Imaging in Primary Hyperparathyroidism;474 11.14.1;INTRODUCTION;474 11.14.2;DUAL-ENERGY X-RAY ABSORPTIOMETRY;474 11.14.3;HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HRPQCT);476 11.14.4;TRABECULAR BONE SCORE;478 11.14.5;CONCLUSION;479 11.14.6;References;480 11.15;Chapter 31 - Primary Hyperparathyroidism and the Kidney;482 11.15.1;INTRODUCTION;482 11.15.2;CO-EVOLUTION OF THE PARATHYROID GLAND AND KIDNEY: FROM WATER TO LAND;483 11.15.3;RENAL CALCIUM REABSORPTION;483 11.15.4;CLINICAL ASSESSMENT OF CALCIUM PROCESSING BY THE KIDNEY;484 11.15.5;RENAL PHOSPHATE REABSORPTION;486 11.15.6;CLINICAL ASSESSMENT OF PHOSPHATE PROCESSING BY THE KIDNEY;486 11.15.7;RENAL BICARBONATE REABSORPTION;488 11.15.8;RENAL PRODUCTION OF 1,25-DIHYDROXYVITAMIN D;488 11.15.9;ROLE OF KIDNEY IN SETTING THE SERUM LEVEL OF CALCIUM AND PHOSPHATE IN PHPT;489 11.15.10;EFFECT OF RENAL FAILURE AND DRUGS ACTING ON THE KIDNEY;489 11.15.11;EFFECT OF TREATMENT OF PHPT ON THE KIDNEY;490 11.15.12;URINARY STONE DISEASE;490 11.15.13;NEPHROCALCINOSIS;492 11.15.14;References;492 11.16;Chapter 32 - Non-traditional Mani
festations of Primary Hyperparathyroidism;496 11.16.1;INTRODUCTION;496 11.16.2;PSYCHOLOGICAL AND COGNITIVE SYMPTOMS AND QUALITY OF LIFE;496 11.16.3;CARDIOVASCULAR DISEASE;500 11.16.4;RHEUMATIC DISEASE;503 11.16.5;GASTROINTENSTINAL DISEASE;503 11.16.6;CANCER;504 11.16.7;CONCLUSIONS;504 11.16.8;References;504 11.17;Chapter 33 - Vitamin D and Primary Hyperparathyroidism;508 11.17.1;CROSS-SECTIONAL STUDIES;508 11.17.2;WHY ARE PRIMARY HYPERPARATHYROIDISM AND LOW VITAMIN D LEVELS SO CONSISTENTLY ASSOCIATED?;509 11.17.3;VITAMIN D SUPPLEMENTATION STUDIES;510 11.17.4;GENERAL CONCLUSIONS;512 11.17.5;References;513 11.18;Chapter 34 - Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism;516 11.18.1;INTRODUCTION;516 11.18.2;METHODS;516 11.18.3;WORKSHOP GROUP #1: DIAGNOSIS OF PRIMARY HYPERPARATHYROIDISM;517 11.18.4;CLINICAL PRESENTATIONS OF PRIMARY HYPERPARATHYROIDISM;518 11.18.5;MANAGEMENT;519 11.18.6;BLUEPRINT FOR FUTURE RESEARCH (ADAPTED FROM REFERENCE 1);522 11.18.7;CONCLUSION;522 11.18.8;Acknowledgments;522 11.18.9;References;523 11.19;Chapter 35 - Preoperative Localization of Abnormal Parathyroid Glands;526 11.19.1;INTRODUCTION;526 11.19.2;ULTRASOUND;527 11.19.3;PARATHYROID SCINTIGRAPHY;531 11.19.4;COMPUTED TOMOGRAPHY;535 11.19.5;MAGNETIC RESONANCE IMAGING (MRI);538 11.19.6;RADIOGUIDED SURGERY;539 11.19.7;CONCLUDING REMARKS;540 11.19.8;References;542 11.20;Chapter 36 - Surgical Management of Primary Hyperparathyroidism;546 11.20.1;INTRODUCTION;546 11.20.2;CLINICAL PRESENTATION TO THE SURGEON AND DIAGNOSTIC CONSIDERATIONS;546 11.20.3;INDICATIONS FOR SURGERY;546 11.20.4;PREOPERATIVE PREPARATION;547 11.20.5;OPERATIVE APPROACHES;548 11.20.6;POSTOPERATIVE MANAGEMENT;552 11.20.7;OUTCOMES OF PARATHYROID SURGERY;552 11.20.8;SPECIAL CONSIDERATIONS;553 11.20.9;SUMMARY;557 11.20.10;References;557 11.21;Chapter 37 - Medical Management of Primary Hyperparathyroidism;560 11.21.1;INTRODUCTION;560 11.21.2;GENERAL MEASURES;560 11.21.3;PHARMACOLOGIC THERAPY;561 11.21.4;S
PECIFIC SITUATIONS;576 11.21.5;References;577 12;Section III - Non-Parathyroid Hypercalcemic States;582 12.1;Chapter 38 - Hypercalcemia Due to PTHrP;584 12.1.1;PTHRP DISCOVERY AND MOLECULAR IDENTIFICATION;584 12.1.2;METABOLISM OF PTHRP;587 12.1.3;CIRCULATING FORMS OF PTHRP;587 12.1.4;PTHRP AS A CLINICAL TARGET;595 12.1.5;SUMMARY;596 12.1.6;References;596 12.2;Chapter 39 - Hypercalcemia Associated with Local and Ectopic Hormone Production;604 12.2.1;1.-HYDROXYLASE;604 12.2.2;25-HYDROXYVITAMIN D-24-HYDROXYLASE;606 12.2.3;SYSTEMIC ELEVATIONS OF CYTOKINES IN MALIGNANCY-ASSOCIATED HYPERCALCEMIA;607 12.2.4;BREAST CANCER;607 12.2.5;MULTIPLE MYELOMA;608 12.2.6;References;609 12.3;Chapter 40 - Genetic Disorders Caused by Mutations in the PTH/PTHrP Receptor and Downstream Effector Molecules;614 12.3.1;INTRODUCTION;614 12.3.2;THE PTH/PTHRP RECEPTOR SYSTEM;614 12.3.3;HUMAN DISORDERS CAUSED BY MUTATIONS IN THE PTH/PTHRP SIGNALING PATHWAY;617 12.3.4;MUTATIONS IN GENES DOWNSTREAM OF THE PTH/PTHRP RECEPTOR;625 12.3.5;CONCLUSIONS;628 12.3.6;References;628 12.4;Chapter 41 - The Differential Diagnosis of Hypercalcemia;634 12.4.1;INTRODUCTION;634 12.4.2;PARATHYROID HORMONE-MEDIATED HYPERCALCEMIA;634 12.4.3;PARATHYROID HORMONE-RELATED PROTEIN-MEDIATED HYPERCALCEMIA;635 12.4.4;MIXED PTHRP AND CYTOKINE-MEDIATED HYPERCALCEMIA;636 12.4.5;1,25-DIHYDROXYVITAMIN D-INDUCED HYPERCALCEMIA;637 12.4.6;OTHER CAUSES OF EXCESSIVE BONE RESORPTION;638 12.4.7;SUPPLEMENT AND DRUG-INDUCED HYPERCALCEMIA;638 12.4.8;OTHER CAUSES OF HYPERCALCEMIA, MECHANISM UNKNOWN;639 12.4.9;AN APPROACH TO THE PATIENT WITH HYPERCALCEMIA;639 12.4.10;References;641 12.5;Chapter 42 - Acute Management of Hypercalcemia;644 12.5.1;INTRODUCTION;644 12.5.2;DIFFERENTAL DIAGNOSIS OF HYPERCALCEMIA;644 12.5.3;PATHOPHYSIOLOGY OF ACUTE HYPERCALCEMIA;645 12.5.4;CLINICAL FEATURES OF HYPERCALCEMIA;647 12.5.5;THERAPY OF ACUTE HYPERCALCEMIA;648 12.5.6;References;653 13;Section IV - Secondary and Tertiary Hyperparathyroid States;658 13.1;Chapter
43 - Vitamin D and Parathyroid Hormone;660 13.1.1;INTRODUCTION;660 13.1.2;THE VITAMIN DCALCIUM HOMEOSTATIC SYSTEM;660 13.1.3;PTH AND VITAMIN D INTERACTIONS IN CALCIUM BALANCE;662 13.1.4;PTH AND VITAMIN D ADEQUACY;663 13.1.5;PTH AND VITAMIN DRECIPROCAL INFLUENCES;665 13.1.6;MAGNESIUM, PTH, AND VITAMIN D;666 13.1.7;References;666 13.2;Chapter 44 - The Parathyroids in Renal Disease: Pathophysiology and Systemic Consequences;668 13.2.1;Pathophysiology and Systemic Consequences;668 13.2.2;INTRODUCTION;668 13.2.3;PATHOGENESIS OF CKD-MBD;668 13.2.4;SYSTEMIC CONSEQUENCES OF ABNORMAL MINERAL METABOLISM IN CKD;671 13.2.5;SUMMARY;674 13.2.6;References;674 13.3;Chapter 45 - Clinical Skeletal Syndromes Associated with Parathyroid Disorders in Chronic Kidney Disease;680 13.3.1;INTRODUCTION AND EVOLUTION OF SECONDARY HYPERPARATHYROIDISM;680 13.3.2;SKELETAL DISEASES ASSOCIATED WITH PARATHYROID HORMONE IN CHRONIC RENAL FAILURE;681 13.3.3;CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD);684 13.3.4;OSTEOPOROSIS;685 13.3.5;BONE MINERAL DENSITY AND USE OF FRAX AT DIFFERENT STAGES OF CKD;685 13.3.6;BIOCHEMICAL MARKERS OF BONE TURNOVER COMBINED WITH PTH IN THE MANAGEMENT OF SKELETAL ABNORMALITIES IN CKD;687 13.3.7;BONE BIOPSY FOR QUANTITATIVE HISTOMORPHOMETRY IN SKELETAL DISORDERS OF CKD;688 13.3.8;TREATMENT OF SKELETAL FRACTURES IN CHRONIC KIDNEY DISEASE;688 13.3.9;CONCLUSIONS;692 13.3.10;References;692 13.4;Chapter 46 - Other Secondary Hyperparathyroid States;698 13.4.1;DISORDERS OF CALCIUM BALANCE;698 13.4.2;PHOSPHATE-WASTING DISORDERS;702 13.4.3;POST-RENAL TRANSPLANT;704 13.4.4;ACIDBASE DISORDERS;705 13.4.5;MEDICATIONS;705 13.4.6;References;706 14;Section V - The Hypoparathyroid States;712 14.1;Chapter 47 - Hypoparathyroidism in the Differential Diagnosis of Hypocalcemia;714 14.1.1;DEFINITION OF THE PROBLEM;714 14.1.2;DIFFERENTIAL DIAGNOSIS OF HYPOCALCEMIA;715 14.1.3;CLINICAL EVALUATION;718 14.1.4;LABORATORY EVALUATION;719 14.1.5;GENE AND ANTIBODY TESTING;720 14.1.6;Referen
ces;721 14.2;Chapter 48 - Magnesium Depletion and Parathyroid Function;724 14.2.1;INTRODUCTION;724 14.2.2;THE CALCIUM-SENSING RECEPTOR;724 14.2.3;THE ROLE OF MAGNESIUM IN CASR FUNCTION;725 14.2.4;CLINICAL MANIFESTATIONS OF MAGNESIUM DEFICIENCY;726 14.2.5;CONDITIONS THAT PRODUCE MAGNESIUM DEFICIENCY;728 14.2.6;HOMEOSTASIS AND FUNCTIONS OF MAGNESIUM;728 14.2.7;DIAGNOSIS OF MAGNESIUM DEFICIENCY;728 14.2.8;THE MAGNESIUM TOLERANCE TEST;729 14.2.9;TREATMENT OF MAGNESIUM DEFICIENCY AND ITS EFFECT ON THE PARATHYROID CALCIUM-SENSING RECEPTOR;729 14.2.10;MAGNESIUM DEPLETION AND VITAMIN D STATUS;730 14.2.11;SUMMARY;731 14.2.12;References;731 14.3;Chapter 49 - Epidemiology of Hypoparathyroidism;734 14.3.1;INTRODUCTION;734 14.3.2;INCIDENCE AND RISK FACTORS;734 14.3.3;PREVALENCE;738 14.3.4;COST;739 14.3.5;HOSPITALIZATION;739 14.3.6;MORBIDITY;739 14.3.7;MORTALITY;741 14.3.8;CONCLUSION;742 14.3.9;References;742 14.4;Chapter 50 - The Molecular Genetics of Hypoparathyroidism;746 14.4.1;INTRODUCTION;746 14.4.2;ISOLATED HYPOPARATHYROIDISM;747 14.4.3;HYPOPARATHYROIDISM ASSOCIATED WITH COMPLEX DISORDERS;751 14.4.4;DIAGNOSTIC WORK-UP IN NON-SURGICAL, IDIOPATHIC HYPOPARATHYROIDISM, PRENATAL DIAGNOSIS, AND GENETIC COUNSELING;756 14.4.5;CONCLUSION;758 14.4.6;References;758 14.5;Chapter 51 - Surgical Hypoparathyroidism;764 14.5.1;INTRODUCTION;764 14.5.2;HYPOPARA AFTER THYROID SURGERY;764 14.5.3;HYPOPARA AFTER PARATHYROID SURGERY;765 14.5.4;CLINICAL MANIFESTATIONS;765 14.5.5;PREDICTING AND PREVENTING SURGICAL HYPOPARATHYROIDISM;766 14.5.6;PARATHYROID AUTOTRANSPLANTATION;767 14.5.7;MANAGEMENT OF IMMEDIATE POSTOPERATIVE HYPOCALCEMIA: OUR PROTOCOL;769 14.5.8;SUMMARY;769 14.5.9;References;769 14.6;Chapter 52 - Autoimmune Hypoparathyroidism;772 14.6.1;INTRODUCTION;772 14.6.2;HISTORY;772 14.6.3;CLINICAL FEATURES OF APS1;773 14.6.4;PATHOGENESIS;777 14.6.5;ETIOLOGY;780 14.6.6;TREATMENT;780 14.6.7;Acknowledgments;782 14.6.8;References;782 14.7;Chapter 53 - Clinical Manifestations of Hypoparathyroidism;
788 14.7.1;INTRODUCTION;788 14.7.2;NEUROLOGIC MANIFESTATIONS;788 14.7.3;CARDIAC MANIFESTATIONS;791 14.7.4;OPHTHALMIC MANIFESTATIONS;792 14.7.5;CUTANEOUS MANIFESTATIONS;792 14.7.6;DENTAL MANIFESTIONS;792 14.7.7;HYPOPARATHYROIDISM-ASSOCIATED MYOPATHY;793 14.7.8;GASTROINTESTINAL MANIFESTATIONS;793 14.7.9;SKELETAL MANIFESTATIONS;793 14.7.10;RENAL MANIFESTATIONS;793 14.7.11;LATENT AND SUBCLINICAL HYPOPARATHYROIDISM;794 14.7.12;PRESENTING SIGNS AND SYMPTOMS;794 14.7.13;References;795 14.8;CHAPTER 54 - Skeletal Manifestations of Hypoparathyroidism;798 14.8.1;INTRODUCTION;798 14.8.2;SKELETAL MANIFESTATIONS OF HYPOPARATHYROIDISM;798 14.8.3;SKELETAL EFFECTS OF PTH TREATMENT IN HYPOPARATHYROIDISM;801 14.8.4;SUMMARY;804 14.8.5;References;805 14.9;Chapter 55 - Molecular and Clinical Aspects of Pseudohypoparathyroidism;808 14.9.1;HISTORY AND NOSOLOGY;808 14.9.2;PTH SIGNAL TRANSDUCTION AND THE ROLE OF G-PROTEINS;810 14.9.3;MOLECULAR BIOLOGY OF THE GNAS GENE;813 14.9.4;TISSUE-SPECIFIC IMPRINTING OF GNAS;814 14.9.5;PATHOPHYSIOLOGY OF PTH RESISTANCE IN PSEUDOHYPOPARATHYROIDISM;815 14.9.6;MOLECULAR CLASSES OF PSEUDOHYPOPARATHYROIDISM;816 14.9.7;MULTIPLE HORMONE RESISTANCE IN PSEUDOHYPOPARATHYROIDISM TYPE 1A;818 14.9.8;CLINICAL FEATURES;819 14.9.9;DIAGNOSIS OF PSEUDOHYPOPARATHYROIDISM;822 14.9.10;TREATMENT;823 14.9.11;CONCLUSION;825 14.9.12;References;825 14.10;Chapter 56 - Treatment of Hypoparathyroidism with Calcium and Vitamin D;834 14.10.1;TREATMENT;835 14.10.2;CONCLUSION;836 14.10.3;References;836 14.11;Chapter 57 - Treatment of Hypoparathyroidism with Parathyroid Hormone;838 14.11.1;INTRODUCTION;838 14.11.2;TREATMENT OF HYPOPARATHYROIDISM WITH PTH(134);838 14.11.3;TREATMENT OF HYPOPARATHYROIDISM WITH PTH(184);840 14.11.4;SUMMARY, AREAS OF UNCERTAINTY, AND FUTURE DIRECTIONS;847 14.11.5;References;849 15;Section VI - The Parathyroids and Osteoporosis;852 15.1;Chapter 58 - Parathyroid Hormone in the Pathophysiology of Osteoporosis;854 15.1.1;INTRODUCTION;854 15.1.2;EARLY POSTMENOPAU
SAL BONE LOSS;854 15.1.3;AGE-RELATED CHANGES IN PTH SECRETION;855 15.1.4;RELATIONSHIP OF AGE-RELATED INCREASES IN SERUM PTH TO INCREASED BONE TURNOVER AND BONE LOSS;857 15.1.5;ETIOLOGY OF THE SECONDARY HYPERPARATHYROIDISM OF AGING;859 15.1.6;SUMMARY AND CONCLUSIONS;860 15.1.7;References;860 15.2;Chapter 59 - Parathyroid Hormone and Glucocorticoid-induced Osteoporosis;864 15.2.1;INTRODUCTION;864 15.2.2;MECHANISM OF GLUCOCORTICOID- INDUCED BONE LOSS;864 15.2.3;MECHANISM OF ANABOLIC ACTION OF PTH ON BONE IN GIOP;864 15.2.4;ROLE OF PTH IN THE PATHOGENESIS OF GIOP;865 15.2.5;TREATMENT OF GIOP WITH PARATHYROID HORMONE;866 15.2.6;CONCLUSION;868 15.2.7;References;868 15.3;Chapter 60 - Parathyroid Hormone as Monotherapy for the Treatment of Osteoporosis;870 15.3.1;INTRODUCTION;870 15.3.2;INDICATIONS FOR PTH THERAPY IN OSTEOPOROSIS;870 15.3.3;MODE OF ACTION;871 15.3.4;PERSISTENCE OF EFFECT;875 15.3.5;RECHALLENGE WITH PTH;875 15.3.6;COST EFFECTIVENESS OF TPTD;875 15.3.7;PTH TREATMENT IN GLUCOCORTICOID-TREATED PATIENTS;876 15.3.8;OTHER POTENTIAL APPLICATIONS FOR PTH TREATMENT;877 15.3.9;CONCLUSION REGARDING OSTEOPOROSIS TREATMENT;877 15.3.10;References;877 15.4;Chapter 61 - Combination Osteoporosis Therapy with Parathyroid Hormone;880 15.4.1;INTRODUCTION;880 15.4.2;COMBINATION OSTEOPOROSIS THERAPY;880 15.4.3;PARATHYROID HORMONE AND ESTROGEN OR SELECTIVE ESTROGEN-RECEPTOR MODULATOR THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS;881 15.4.4;PARATHYROID HORMONE AND BISPHOSPHONATES IN POSTMENOPAUSAL OSTEOPOROSIS;881 15.4.5;PARATHYROID HORMONE AND DENOSUMAB IN POSTMENOPAUSAL OSTEOPOROSIS;884 15.4.6;COMBINATION THERAPY IN MALE OSTEOPOROSIS;884 15.4.7;PARATHYROID HORMONE AFTER ANTIRESORPTIVE THERAPY;885 15.4.8;ANTIRESORPTIVE THERAPY AFTER PARATHYROID HORMONE;886 15.4.9;HYPERCALCEMIA AND HYPERCALCIURIA WITH COMBINATION THERAPY;887 15.4.10;SUMMARY;887 15.4.11;References;888 15.5;Chapter 62 - The Role of Parathyroid Hormone in Fracture Healing;892 15.5.1;THE BIOLOGY OF FRACTURE REPAIR;892 15.5.2;
THE ROLE OF PTH IN PRE-CLINICAL MODELS OF FRACTURE HEALING;895 15.5.3;THE ROLE OF PTH IN CLINICAL MODELS OF FRACTURE HEALING;899 15.5.4;THE EFFECT OF PTH WITH ADDITIONAL ADJUVANTS;901 15.5.5;CONCLUSIONS;902 15.5.6;References;902 15.6;Chapter 63 - Parathyroid Function and Disease during Pregnancy, Lactation, and Fetal/Neonatal Development;904 15.6.1;INTRODUCTION;904 15.6.2;MINERAL PHYSIOLOGY DURING PREGNANCY;904 15.6.3;MINERAL PHYSIOLOGY DURING FETAL DEVELOPMENT;907 15.6.4;MINERAL PHYSIOLOGY DURING LACTATION;908 15.6.5;MINERAL PHYSIOLOGY IN THE NEONATE;911 15.6.6;PARATHYROID DISORDERS DURING PREGNANCY;912 15.6.7;PARATHYROID DISORDERS DURING LACTATION;917 15.6.8;PARATHYROID DISORDERS DURING FETAL AND NEONATAL DEVELOPMENT;919 15.6.9;CONCLUSIONS;922 15.6.10;References;923 16;Index;930
